Gene knockouts in mice are enormously useful for determining the biological functions of their encoded proteins in the whole animal. However, because many genes are expressed in a multitude of tissues throughout development, it is difficult to determine, for example, the function a particular gene product in the adult if the knockout is embryonic lethal. This problem can be circumvented by tissue-specific gene knockouts using the Cre recombinase/loxP system. The goal of this Core is to knockout the CPEB gene in the adult brain, specifically the CA1 region of the hippocampus. To do this, homologous recombination in ES cells will be used to insert loxP sites into introns of the CPEB gene. Mice containing this recombined gene will have a normal CPEB gene and protein. However, when these mice are mated with other mice containing a Cre recombinase transgene under the regulation of the CaMKII promoter, adults will undergo a recombination event at the CPEB locus in the CA1 region of the hippocampus. These mice will effectively be null for CPEB. This Core will construct the targeting vector for CPEB recombination, electroporate and screen ES cells, inject blastocysts, perform the embryo transfer, and perform all the genotyping. The Core will also maintain several lines of mice as they pertain to these experiments. These mice will be analyzed at the molecular, cellular, neurophysiological, and behavioral levels. The results obtained with these mice will have important implications for brain function, including learning and memory.